Trait‐mediated indirect interactions: Moose browsing increases sawfly fecundity through plant‐induced responses

1. Induced responses in plants, initiated by herbivory, create potential for trait‐mediated indirect interactions among herbivores. Responses to an initial herbivore may change a number of plant traits that subsequently alter ecological processes with additional herbivores. Although common, indirect interactions between taxonomically distant herbivores, such as mammals and insects, are less studied than between taxonomically related species (i.e., insect–insect). In terms of mammal– insect interactions, effects on insect numbers (e.g., density) are relatively well studied, whereas effects on performance (e.g., fecundity) are rarely explored. Moreover, few studies have explored mammal–insect interactions on coniferous plants. 2. The aim of this study was to investigate the effect of mammalian induced responses on insect performance. We specifically investigated the effect of moose (Alces alces) browsing on Scots pine (Pinus sylvestris) and subsequent effects on sawfly (Neodiprion sertifer) performance. 3. Sawfly larvae were reared on browsed, clipped, and unbrowsed control pine trees in a controlled field experiment. Afterward, cocoon weight was measured. Needle C:N ratio and di‐terpene content were measured in response to browsing. 4. Sawfly performance was enhanced on trees browsed by moose. Cocoon weight (proxy for fecundity) was 9 and 13% higher on browsed and clipped trees compared to unbrowsed trees. Cocoon weight was weakly related to needle C:N ratio, and browsed trees had lower a C:N ratio compared to unbrowsed trees. Needle di‐terpene content, known to affect sawfly performance, was neither affected by the browsing treatments nor did it correlate with sawfly weight. 5. We conclude that mammalian herbivory can affect insect herbivore performance, with potential consequences for ecological communities and with particular importance for insect population dynamics. The measured plant variables could not fully explain the effect on sawfly performance providing a starting point for the consideration of additional plant responses induced by mammalian browsing affecting insect performance

A phase 2 trial investigating the efficacy and safety of the mPGES-1 inhibitor vipoglanstat in systemic sclerosis-related Raynaud's

OBJECTIVE: Our objective was to test the hypothesis, in a double-blind, placebo-controlled study that vipoglanstat, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) which decreases prostaglandin E2 (PGE2) and increases prostacyclin biosynthesis, improves RP.METHODS: Patients with systemic sclerosis (SSc) and ≥7 RP attacks during the last screening week prior to a baseline visit were randomised to four weeks treatment with vipoglanstat 120 mg or placebo. A daily electronic diary captured RP attacks (duration and pain) and Raynaud's Condition Score, with change in RP attacks/week as primary end point. Cold challenge assessments were performed at baseline and end of treatment. Exploratory endpoints included patients' and physicians' global impression of change, Assessment of Scleroderma-associated Raynaud's Phenomenon questionnaire, mPGES-1 activity, and urinary excretion of arachidonic acid metabolites.RESULTS: Sixty-nine subjects received vipoglanstat (n = 33) or placebo (n = 36). Mean weekly number of RP attacks (baseline; vipoglanstat 14.4[SD 6.7], placebo 18.2[12.6]) decreased by 3.4[95% CI -5.8;-1.0] and 4.2[-6.5;-2.0] attacks per week (p= 0.628) respectively. All patient reported outcomes improved, with no difference between the groups. Mean change in recovery of peripheral blood flow after cold challenge did not differ between the study groups. Vipoglanstat fully inhibited mPGES-1, resulting in 57% reduction of PGE2 and 50% increase of prostacyclin metabolites in urine. Vipoglanstat was safe and well tolerated.CONCLUSION: Although vipoglanstat was safe, and well tolerated in a dose achieving full inhibition of mPGES-1, it was ineffective in SSc-related RP. Further development and evaluation of vipoglanstat will therefore be in other diseases where mPGES-1 plays a pathogenetic role.</p

A phase 2 trial investigating the efficacy and safety of the mPGES-1 inhibitor vipoglanstat in systemic sclerosis-related Raynaud's

OBJECTIVE: Our objective was to test the hypothesis, in a double-blind, placebo-controlled study that vipoglanstat, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) which decreases prostaglandin E2 (PGE2) and increases prostacyclin biosynthesis, improves RP.METHODS: Patients with systemic sclerosis (SSc) and ≥7 RP attacks during the last screening week prior to a baseline visit were randomised to four weeks treatment with vipoglanstat 120 mg or placebo. A daily electronic diary captured RP attacks (duration and pain) and Raynaud's Condition Score, with change in RP attacks/week as primary end point. Cold challenge assessments were performed at baseline and end of treatment. Exploratory endpoints included patients' and physicians' global impression of change, Assessment of Scleroderma-associated Raynaud's Phenomenon questionnaire, mPGES-1 activity, and urinary excretion of arachidonic acid metabolites.RESULTS: Sixty-nine subjects received vipoglanstat (n = 33) or placebo (n = 36). Mean weekly number of RP attacks (baseline; vipoglanstat 14.4[SD 6.7], placebo 18.2[12.6]) decreased by 3.4[95% CI -5.8;-1.0] and 4.2[-6.5;-2.0] attacks per week (p= 0.628) respectively. All patient reported outcomes improved, with no difference between the groups. Mean change in recovery of peripheral blood flow after cold challenge did not differ between the study groups. Vipoglanstat fully inhibited mPGES-1, resulting in 57% reduction of PGE2 and 50% increase of prostacyclin metabolites in urine. Vipoglanstat was safe and well tolerated.CONCLUSION: Although vipoglanstat was safe, and well tolerated in a dose achieving full inhibition of mPGES-1, it was ineffective in SSc-related RP. Further development and evaluation of vipoglanstat will therefore be in other diseases where mPGES-1 plays a pathogenetic role.</p